Cognitive complaints have been anecdotally reported among women receiving adjuvant chemotherapy for breast cancer, and recently this has been subjected to more rigorous study. Cerebral functioning can be assessed by self-report, standardized neuropsychological testing, and through examination of brain metabolism (all of which have been studied in our laboratory). The literature suggests a relationship between chemotherapy exposure and poorer performance on neurocognitive testing; however, patients with cognitive complaints do not necessarily test poorly and their complaints are often associated with symptoms of depression and anxiety. Preliminary work in our laboratory suggests that hormonal changes associated with menopause and adjuvant endocrine therapy for breast cancer also influence the effects of chemotherapy on cognitive functioning. Little is known about the potential mechanisms by which adjuvant endocrine therapy influences cerebral functioning after breast cancer treatment, and in this study we will address this question by studying women who have recently completed their primary breast cancer treatments (surgery, radiation, chemotherapy) and who are about to initiate adjuvant endocrine therapy (with tamoxifen or aromatase inhibitors). We will examine the potential mechanisms by which endocrine therapy affects cerebral functioning, by consideration of a comprehensive framework that includes the role of constitutional symptoms (fatigue, depression, anxiety), and immune alterations, in addition to specific cancer treatments (chemotherapy, hormonal treatments), and endogenous endocrine exposures (estrogen, cortisol). In this longitudinal, observational cohort study, we propose the following specific aims: 1)To evaluate the effects of adjuvant endocrine therapy on cognitive functioning through standardized questionnaires and neuropsychological assessments in 260 breast cancer patients at the end of primary treatment (baseline) when endocrine treatment is initiated, and one year later (follow-up). 2)To examine the association between cognitive functioning and measures of cerebral metabolism by obtaining positron emission tomography (PET) brain imaging, at rest and with a memory challenge, in close temporal proximity to the baseline assessment of cognitive functioning in a subset of 60 women, with a follow-up assessment one year later. 3)To explore the biopsychosocial mechanisms by which adjuvant endocrine therapy influences cerebral functioning by examining changes in cognitive functioning and brain metabolism, and their relationship to immune and endocrine function, mood and symptoms between the baseline and follow-up assessment one year later. Lay summary: Breast cancer is the most common cancer in women. After treatments for breast cancer, some women complain of difficulty in concentrating and thinking. This study will examine the effects of breast cancer treatments on cognitive, psychological, immune and endocrine function to try to understand the biological mechanisms of these complaints so that they may be better prevented or treated in the future. [unreadable] [unreadable]